Syphilis is an infectious disease caused by the Treponema pallidum bacterium, transmitted mainly through sexual con tact but sometimes by the transplacental route and during passage through the birth canal. Syphilis can therefore be defined as:

• Acquired, when contracted after birth

 • Congenital or prenatal, when contracted transplacentally

 • Connatal, when acquired at the time of passage through the birth canal

Syphilis develops in several stages, each characterized by different symptoms and courses.

In the primary stage, after an incubation period of about 3 weeks, a painless lump (a complicated ulcer or syphiloma) appears at the point of inoculation of the bacterium (generally the genitals). Usually, the syphiloma disappears even if it is not treated, but after 6 weeks, if the disease is not treated, it evolves into the secondary stage. The latter is characterized by the invasion of the bacterium throughout the body, resulting in unaccompanied rashes, itching, fever, enlarged lymph nodes, patchy alopecia, headache, weight loss, myalgia, and fatigue. These skin manifestations disappear after 1–2 weeks but recur over the years (latent stage). Without appropriate treatment, lesions in the internal organs, especially in the central nervous system, may occur after years; in the tertiary stage, the spinal cord will be affected (motor disorders), and in the last stage, the brain (dementia).

Maternal–fetal transmission can occur at any time during pregnancy, but the risk of transmission is most significant from the third month and increases as gestation progresses. The stage of the mother’s syphilis is the most critical factor in determining the probability of vertical transmission. Primary or secondary syphilis, if untreated, carries a risk of fetal transmission of 70–100%, if treated, 2%; in case of early latent syphilis, 40–83%; and 2.5–10% in the late latent infection stage.

Early treatment of the mother with penicillin theoretically eliminates the risk of vertical transmission of the disease as long as the interval between initiation of therapy and delivery is >4 weeks. The severity of untreated fetal infection is greater the earlier the infection. Therefore, prevention and diagnosis of congenital syphilis depend on the infection’s diagnosis and treatment in the pregnant woman.

The neonatal consequences of vertical transmission include not only congenital syphilis, which is characterized by developmental alterations in the child if left untreated, but also obstetrical complications such as late abortion, death in utero, fetal hydrops, and preterm delivery.

Two types of tests can be used for serological screening:

• Nonspecific treponema tests, based on the detection of IgG and IgM antibodies directed against substances released by the tissues due to the pathogenic action of treponema, defined as antilipoid antibodies. Among these, the most commonly used are the rapid plasma reagin (RPR) and the venereal disease research laboratories (VDRL).

• Treponema-specific tests, based on the detection of antibodies to Treponema pallidum-specific antigens.

VDRL is a simple test based on a flocculation reaction between the patient’s serum and particular types of lipids, known as cardiolipins. RPR is a technical variant of VDRL in which the addition of micro carbon particles modifies the antigen. Both techniques are easy to perform, inexpensive, and characterized by high sensitivity and low specificity; a false-positive result can be observed in cases of infectious diseases such as malaria, tuberculosis, viral fevers, trypanosomiasis, and leprosy and in other conditions such as pregnancy, collagenopathies, advanced age, and drug addiction. Treponema-specific tests include the Treponema Pallidum Haemagglutination Assay (TPHA) and the Treponema Pallidum Particle Agglutination Assay (TPPA), which are positive 2–4 weeks after infection and have a sensitivity ranging from 60% to 99% (low sensitivity only at disease onset) and a specificity >99%, and immunoassays, such as the enzyme immunoassay (EIA) and the chemiluminescence assay (CLIA). EIA (with recombinant antigens) is positive 3 weeks after infection, with a sensitivity >98% and specificity >97%; CLIA is positive 3 weeks after infection, with a sensitivity and specificity >98% and >97%, respectively; fluorescent treponemal antibody absorption (an immunofluorescence test with adsorption, currently little used) has a sensitivity of 84% in primary syphilis and about 100% in the other stages, and a specificity of 96%. While for nonspecific tests, the titer of positivity correlates with disease activity and response to therapy, treponema-specific tests generally remain positive throughout life, regardless of therapy and disease activity.

Syphilis in pregnancy is a largely preventable cause of neonatal morbidity and mortality through screening and treatment of the infection in the mother. Diagnosis and staging of syphilis in pregnant women are based on clinical examination and serological testing. The serological screening test is a treponema-specific test (TPHA, TPPA, EIA, or CLIA). A second specific test must confirm positivity of one specific test. If the diagnosis of syphilis is confirmed, a nonspecific test (RPR or VDRL) should be performed to deter mine the stage of infection.

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